It is infrequently recognized that lung infections are the leading cause of combined morbidity and mortality worldwide (1). A diverse array of microbes and viruses are responsible for causing lower respiratory tract infections. Pathogenic bacteria account for a large proportion of these diseases including community acquired pneumonia, hospital acquired pneumonia, and ventilator associated pneumonia, which together affect more than 4 million people in the United States annually (2, 3). Globally, tuberculosis continues to be a devastating disease killing more than 1.7 million people in 2004, according to the World Health Organization. In addition to being causative agents, bacterial infections of the lung are closely associated with morbidity and mortality in numerous diseases of nonbacterial origins. Examples include chronic obstructive pulmonary disease, bronchiectasis, diffuse panbronchiolitis, cystic fibrosis, and acute respiratory distress syndrome. Combined, these bacterial pulmonary infections represent a significant threat to US and global human health.
Analysis of disability-adjusted life years (a combined measure of morbidity and mortality) has revealed that the global disease burden caused by lung infections decreased little if any from 1990 to 2002, even in the world's wealthiest nations (1). Analysis of annual United States deaths from lung infections indicates that mortality rates have not improved since prior to 1950 (4). In fact, deaths from pneumonia and influenza increased by more than 50% from 1980 to 1996. While the lack of progress in treating lung infections is a complex issue dependent on numerous variables, one key element of this medical stigma is the emergence of bacterial resistance to antibiotics (5). The natural products and synthetic derivatives that have been mainstays of antimicrobial therapy (i.e. agents with selective toxicity for gram-positive bacteria, gram-negative bacteria, and/or fungi) for more than 60 years are becoming more and more ineffectual, as their ribosomal and enzyme targets accumulate adaptive mutations and resistance elements spread by horizontal gene transfer, both driven by the selective pressure of wide spread antibiotic use. The imperative for the medical and pharmaceutical communities to develop new antimicrobial agents is clear.
Accordingly, there remains a need for treatments for microbial and viral infections, such as respiratory infections.